{"doi":"10.3389/fphar.2019.01540","title":"Bactericidal Activity of Lipid-Shelled Nitric Oxide-Loaded Microbubbles","abstract":"The global pandemic of antibiotic resistance is an ever-burgeoning public health challenge, motivating the development of adjunct bactericidal therapies. Nitric oxide (NO) is a potent bioactive gas that induces a variety of therapeutic effects, including bactericidal and biofilm dispersion properties. The short half-life, high reactivity, and rapid diffusivity of NO make therapeutic delivery challenging. The goal of this work was to characterize NO-loaded microbubbles stabilized with a lipid shell and to assess the feasibility of antibacterial therapy in vitro. Microbubbles (MB) were loaded with either NO alone (NO-MB) or with NO and octafluoropropane (NO-OFP-MB) (9:1 v/v and 1:1 v/v). The size distribution and acoustic attenuation coefficient of NO-MB and NO-OFP-MB were measured. Ultrasound-triggered release of the encapsulated gas payload was demonstrated with 3-MHz pulsed Doppler ultrasound. An amperometric micro-electrode sensor was used to measure NO concentration released from the microbubbles and compared to an NO-OFP-saturated solution. The effect of NO delivery on the viability of planktonic (free living) Staphylococcus aureus (SA) USA 300, a methicillin-resistant strain, was evaluated in a 96 well-plate format. The co-encapsulation of NO with OFP increased the total volume and attenuation coefficient of microbubbles. The NO-OFP-MB were destroyed with a clinical ultrasound scanner at an output with an MI of 1.2 but maintained their echogenicity at an MI of 0.04. The NO dose in NO-MB and NO-OFP-MB was more than 2-fold higher than the NO-OFP-saturated solution. Delivery of NO-OFP-MB increased bactericidal efficacy compared to the NO-OFP-saturated solution or air and OFP-loaded microbubbles. These results suggest that encapsulation of NO with OFP in lipid-shelled microbubbles enhances payload delivery. Furthermore, these studies demonstrate the feasibility and limitations of NO-OFP-MB for antibacterial applications.","journal":"Frontiers in Pharmacology","year":2020,"id":81756,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":422392,"name":"Himanshu Shekhar","orcid":"0000-0003-1226-4196","position":1,"is_corresponding":false},{"id":422393,"name":"Warunya Panmanee","orcid":"0009-0003-3370-2746","position":2,"is_corresponding":false},{"id":422394,"name":"Sydney D. Collins","orcid":"0009-0006-6578-6827","position":3,"is_corresponding":false},{"id":422395,"name":"Arunkumar Palaniappan","orcid":"0000-0002-6510-7760","position":4,"is_corresponding":false},{"id":423284,"name":"Cameron T. McDaniel","orcid":null,"position":5,"is_corresponding":false},{"id":422396,"name":"Daniel J. Hassett","orcid":"0000-0003-2300-4955","position":6,"is_corresponding":false},{"id":232454,"name":"Christy K. Holland","orcid":"0000-0003-3382-7170","position":7,"is_corresponding":false},{"id":422391,"name":"Maxime Lafond","orcid":"0000-0001-8954-9099","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T21:52:58.921847Z","pmid":"32082143","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}